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《Journal of Clinical Neurology》 2006-05
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Applying Lactacystin,a selective proteasome inhibitor,to set up the rat model of Parkinson's disease with Lewy body

ZHANG Ke-zhong,JIANG Yu-ping,DING Xin-sheng. Department of Neurology,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China  
Objective To set up the Parkinson's disease(PD)rat model with pathologic characteristic of Lewy body in nigral cells.Methods SD rats were injected respectively with 8 mg Lactacystin(Lactacystin group),sodium saline(NS group)and 12 mg 6-OHDA(6-OHDA group)by stereotaxic unilateral injection into the pars compacta of substantia nigral.The spontaneous and apomorphine-induced contralateral behaviors of rats were observed.The changes of midbrain histology were viewed by microscope;expression of α-synuclein and tyrosine hydroxylase(TH)positive cells were investigated by immunohistochemistry.The contents of dopamine and homovanillic acid in striatum were determined.Results Rats of NS group did not display abnormal behavior.The animals treated with Lactacystin developed progressively bradykinesia,hypokinesia,tremor,contralateral head tilting,and displayed apomorphine-induced contralateral rotation behavior;3 weeks later the number of TH positive cells were decreased by 83.29% compared with NS group(P0.01),some of which contained Lewy body with intense immune response to α-synuclein.The contents of dopamine and homovanillic acid in Lactacystin group(154.82±37.17,98.66±18.81)were less than those of in NS group in striatum(all P0.01).The rats of 6-OHDA group displayed behavior similar to those of Lactacystin group;the number of nigral cells decreased significantly but no Lewy body.Conclusion The rat model of Parkinson's disease with Lewy body is set up by using Lactacystin which can block the α-synuclein degradation.
【CateGory Index】: R-332
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